Organic compounds



nited m Patent-"TO- 2,812,334 ORGANIC COMPOUNDS This invention relatesto novel spiro[cycloalkane-l,2'-'

pyrrolidyl-l'J-alkyl esters ofdisubstitutedace'tic acids. Thisapplication is a continuation-in-part of application Serial No. 522,847,filed July 18, 1955.

This invention has among its objects the provision of novelspiro[cycloalkane 1,2 pyrrolidyl 1'] alkyl esters of disubstitutedacetic acids, which can exist in the form of the free bases orcoordination complexes thereof such as the amine oxides, quaternaryammonium compounds, acid addition salts and the amine oxide acidaddition salts. The novel compounds of this invention have the followinggeneral structural formula:

y El! RI wherein substituents A and B are the same or-ditferenthydrocarbon radicals such as alkyl,alkenyl, cycloalkyl, cycloalkenyl,aralkyl, or. aryl, preferably being lower hydrocarbon radicals havingfrom one to twelve carbon atoms, inclusive. Sustituents A and B can besubstituted by groups such as halogen, amino, lower-alk'oxy, andthe'like. Examples of substituents A and B are methyl, ethyl, propyl, butyl,octyl, dodecyl, 2-chloroethyl, allyl, butenyl, cyclohexyl, cyclopentyl,cyclohexenyl, cyclopentenyl, benzyl, phenethyl, pchlorobenzyl, phenyl,p-biphenylyl, tolyl, xylyl, p-aminophenyl, p-propoxyphenyl,o,o-dimethyl-p-propoxyphenyl, and the like. R and R" are hydrogen ormethyl, m is a whole number from one to two, inclusive, n is a wholenumber from two to six, inclusive and -cnH2n is a lower alkylene radicalhaving at least two carbon atoms between the valences.

The novel compounds of this invention possess 'pronounced uterinestimulatory properties characterized by prolonged action. They areinactive as diuretics and possess no or very little other knowndetrimental side effects. The quaternary ammonium compounds, e."g., themethobrornides, ethochlorides, methosulfates, and the likeexhibitqualitatively good ganglionic activity in the pharmacodynamic assay,without outstanding anticholinergic action.

The compounds of this invention are prepared by esterityingZ-spiropyrrolidylalkanols of the formula:

wherein R, R, m, n, and C1 tH2n have the values set forth above, with adisubstituted acetic acid halide:

- 2 wherein A and B have the values given above and X is chlorine orbromine. The esterification is preferably accomplished in an inertsolvent such'as benzene using conventional esterifying conditions.

The 2-spiropyrrolidylalkanols can be prepared by the following series ofreactions: 1

CH2-0H2 H g CH:CH2 CH:- R' OHF -R v l /l /1 i non-0H, 0. Ham-on. No. R

I II

=on R= .OCH:'

(OHzM-GH: Iii

i i R our-43H:

1 .Q OH "-011 0 hath-on V p in which R", R", m, n, and CnH2nhave thevalues stated above, and R islower-alkoxy, preferably methoxy.

or ethoxy, or methyl. 7

Suitable disubstituted acetic acid halides are described 1) i-CH:

IV III by Kollolf et al., J. Am. Chem. Soc., 70, 3862 (1948);

ibid., 72, 1650 (1950); and U. S Patent 2,655,511., Others includesisobutyric acid chloride, isobutyric acid bromide, diethylacetic acidchloride, diethylacetic acid bromide, methyl isohexyl acetic acidchloride, methyl isoamyl acetic acid chloride, ethyl butyl' acetic acidchloride, methyl propyl acetic acid chloride, propyl allyl acetic acidchloride, and the like. p

The novel compounds.ofthisinvention are usually administered orally,preferably as an acid addition salt, e. g., hydrochloride, hydrobromide,hydrio'dide, sulfate, citrate, acetate, succinate, nitrate; or as aquaternary ammonium salt, e. g., methobromide, methiodide, ethochloride;or as an amineoxide (prepared by oxidation of these compounds with aperacid or hydrogen peroxide) or addition salt thereof, etc. Suitableforms include tablets, stable aqueous solutions, elixirs, etc, i I I Thepreparation of the compounds of Formula V involves the conversion of anitrocycloalkane (l) to a spiro substituted-pyrrolidine (IV). Incarrying out the first step of this conversion, a nitrocycloalkane (I)is COD. densed with an olefinic compound, preferably an alkyl. acrylate,represented by the following formula:

CH2=(IJ(ILJR wherein R and R have the values given hereinbefore andespecially wherein R is lower-alkoxy, preferably methoxy' or ethoxy, andR is hydrogen, to producea l-(fi car bonylethyl). nitrocycloalkanerepresented by Formula II. The reaction conditions described by Mofi'ettand White,v J. Org. Chem., 17, 407 1952) can be employed using acondensing catalyst, preferably aqueous benzyltrimethylammoniumhydroxide, sodium hydroxide, potassium hydroxide, or other strong base.Other bases, e. g., piperidine, pyrrolidine, morpholine, can also beused. The resulting product (11) can then be isolated and purified, e.g., in the manner described hereinafter, or the reaction mixture freedof solventand; used without isolation'in the subsequent reductionreaction.

v v Patented Nov 5,1957

In the reduction step, a compound represented by Forniula His'reduetivel'y cycliied to produce a spire-pyrrolidine (IV) when R ismethylor a spiropyrrolidone (111) when R is lower-alkoxy. In the formercase, the cyclization is accomplishedwithhydrogen' and a hydrogenationcatalyst, e. g., Raney nickel, etc. In the lattercase, the hydrogenationis accomplished by hydrogenation with a suitable catalyst, e. g., inthemanne'r described by Motfett and White (loc. cit.) and as describedhereinafter, or by chemical means, e. g., zinc or iron in the'presenceof acid.

The conversion of a spiropyrrolidone (III) to a spiropyrrolidine (IV)can be accomplished with lithium aluminum hydride, or other chemicalreducing agent capable of reducing a pyrrolidone to a pyrrolidine, or byhigh pressure hydrogenation according to techniques known in the art.

The alkylation of a spiropyr'rolidine (IV) to an N-w-hydroxy-alkyl-spiropyrrolidine (V) can be accomplished by heating aspiropyrrolidine (IV) with a halohydrin,

e. g., ethylene chlorohydrin, ethylene bromohydrin, propylenechlorohydrin, trimethylene chlorohydrin, etc., an alkylene oxide, e. g.,ethylene oxide, propylene oxide, in the presence or absence of asolvent, or a halo ester followed by reduction of the thus-producedpyrrolidyl al kanoic acid ester with lithium aluminum hydride, e. g.,according to methods known in the art [Moffett, J. Org. Chem., 14, 862(1949) and previouspapers referred to therein], to produce a 2-siprosubstituted pyrrolidylalkanol (V) of the present invention. Examples ofthese alkanols include those represented by Formula V wherein thepyrrolidyl substituted alkanol group is ethanol, propanol,l-methyl-ethanol, l-rnethylpropanol, Z-methylpropane],1,2-dimethylpr'opanol, 1,3 dimetliylpropanol, 2,3-dir'nethylpropanol,1,2,3-trimethylpropanol, butanol, pentanol, hexanol,2,3-dimethylbutanol, l-methylpentanol, etc. group.

The following preparations and examples are illustrative of the processand products of the present invention but are not to be construed aslimiting.

PREPARATION 1.--METHYL p-(l-mrnocycronnxrm- PRoP'IoNATIz In a one-liter,three-necked fia'sk fitted with stirrer, dropping funnel and thermometerwere placed 333 grams (2.55 moles) of nitrocyclohexane (technical grade,redistilled), 300 milliliters of dioxane (lithium aluminumhydride-treated and redistilled.) and thirty milliliters of a 35 percentmethanolic solution of benz'yltrir'nethylammonium hydroxide. To theresulting stirred mixture was added 227.5 grams (2.55 moles) of methylacrylate (redistilled) over a period of fifteen minutes, during whichtime the temperature rose to above 100 degrees centigrade. When thetemperature had dropped to about 55 degrees centigrade, the mixture washeated on a steam bath with stirring for three hours and then maintainedat room temperature for about eighteen hours. The mixture was thendiluted with about one liter of ether, acidified with dilutehydrochloric acid, extracted twice with a saturated aqueous sodiumchloride solution, then with an aqueous sodium chloride solutioncontaining a little sodium bicarbonate and finally with saturatedaqueous sodium-chloride solution. The organic layer was separated, driedand distilled through a Vigreaux column.- There was thus obtained 523.3grams, a yield of 96.8 percent of the theoretical, of methyll-nitrocyclohexyl)-propionate distilling at between 96.5 degreescentigrade at a pressure of 0.05 millimeter of mercury absolute to 124.5degrees at a pressure of 0.35 millimeter and having an n 3- of 1.4710. Asample was redistilled through a six-inch,

helix-packed column to give a fraction boiling at 96 degrees centigradeat 0.025 millimeter pressure and having the analysisbelow V p 7 p QCwHuNQs; 95 -39 N, Found: C, 56.05; H, 8.02; N,:6.48.

PREPARATION 2.SPIRO [CYCLOHEXANE-l,2'- PYRROLIDONE-5 A solution of 453.3grams (2.11 moles) of methyl fl-(l-nitrocyclohexyl)-propionate in 1.26liters of methanol-denatured ethanol (3A) was hydrogenated in thepresence of Raney nickel catalyst for eighteen hours at fifty degreescentigrade. The mixture was cooled, filtered and the filtrate distilledto dryness at reduced pressure. The white crystalline residue wasdissolved in two liters of boiling methylcyclohexane which was thendistilled until about 100 milliliters had been collected, to remove anyresidual ethanol. The solution was clarified by pressure filtrationwhile hot and then cooled. There was thus obtained 253 grams, a yield of72 percent of the theoretical, of spirolcyclohexane 1,2 pyrrolidone 5']melting at 131 to 133 degrees centigrade. A further 31.4 grams ofproduct melting at 129 to 132 degrees centigrade was obtained byconcentration of the mother liquor. A sample recrystallized fromSkellysolve B (hexanehydrocarbons) melted at 132 to 133 degreescentigrade and had the analysis below.

Calculated for C9H15NO: N, 9.14. Found: N, 9.03.

The product is a very weak base moderately soluble in water,.verysoluble in dilute mineral acids and unaffected by boiling twenty percentsodium hydroxide or sulfuric acid.

PREPARATION 3.--SPIRO[CYCLOHEXANE-1,2'ePYRROLIDINE] A mixture of grams(2.5 moles) of lithium aluminum hydride and 1.5 liters oftetrahydrofuran (distilled from lithium aluminum hydride) was refluxedwith stirring for a few minutes and then a solution of 206 grams (1.343moles) of spiro[cyclohexane 1,2 pyrrolidone- 5] dissolved in 1.1 litersof tetrahydrofuran was slowly added. The stirred mixture was then heatedat its refluxing temperature for eighteen hours. About two liters ofsolvent was removed by distillation and the following were slowly addedto the residue in succession: one liter of U. S. P. ether, 200milliliters of ethyl acetate, and one liter of concentrated hydrochloricacid dissolved in 1.5 liters of water. The strongly acidic solution wassteam distilled until a distillation temperature of degrees centigradewas reached. To the hot residue was added about 1,760 grams of aqueousfifty percent sodium hydroxide. The mixture was then steam distilleduntil practically no basic material came over with the distillate. Thefour liters of basic distillate was extracted twice with about one-literportions of ether. The extracted aqueous layer was then subjected tocontinuous extraction with ether for six hours. The combined etherextracts were thoroughly dried withanhydrous potassium carbonate.

This procedure was followed on another run employing 83.5 grams oflithium aluminum hydride, 168.5 grams of spirolcyclohexane-l, 2pyrrolidone 5'} and two liters of tetrahydrofuran.

The combined runs were distilled through a twelve-inch column packedwith fis-inch helices. After the solvent had been removed, the residuewas distilled at reduced pressure. There was obtained a 286 gramfraction of spirolcyclohexane 1,2 pyrrolidine) distilling at 99 to 104degrees centigrade at a pressure of 42 millimeters of mercury absoluteand having an 12 of 1.4817 and the analysis below.

Calcd. for CsHrzN: C, 77.63; H, 12.31; N, 10.06. Found: C, 77.95; H,11.88; N, 9.24.

PREPARATION 4.fi-SPIRO[CYCLOHEXANE-l,2'-PYRROLIDYL- 1 ']-ETHANOL Astirred mixture of 27.84 grams (0.2 mole) of spiro-[cyclohexane-l,2'-pyrrolidine]and 16.1 grams (0.2 mole) of ethylene.chlorohydrin in a 100-milliliter, round-bottomed flask fitted with athermometer, reflux condenser and magnetic stirrer was rapidly heated todegrees centigrade. The heat was removed as the mixture spontaneouslyrose to about 167 degrees centigrade. When the temperature had droppedto 120 degrees centigrade, the flask was again heated at 130 to 150degrees centigrade for fifteen minutes. The cooled solution was mixedwith thirty milliliters of aqueous fifty percent sodium hydroxide andthen extracted thoroughly with four portions of ether. The combinedether extracts were dried with potassium carbonate, filtered and theether removed by distillation. The residue was distilled through asixinch column packed with /e-inch helices. After a forerun ofspiro[cyclohexane-l,2'-pyrrolidine] was removed, there was obtained 23.3grams of fi-spiro[cyclhexane-l,2'- pyrrolidyl-I'Pethanol distilling at138 degrees centigrade at an absolute pressure of twelve millimeters ofmercury. A sample taken from the center out of the distillate had an nof 1.5010 and the analysis below.

Calcd. for C11H21NO: C, 72.08; H, 11.55; N, 7.64. Found: C, 72.41; H,11.87; N, 7.66.

B-Spiro [cyclohexane-1,2-pyrrolidyl-1'] -ethanol hydrochloride wasprepared by adding an excess of anhydrous hydrogen chloride to a cooledsolution of B-spiro [cyclohexane-l,2'-pyrrolidyl-1']-ethanol in benzene.The precipitated, crystalline hydrochloride was filtered. A samplerecrystallized from isopropyl alcohol gavespirolcyclohexane-1,2'-pyrrolidyl-1']-ethano1 hydrochloride melting at177.5 to 179 degrees centigrade and having the analysis below.

. Calcd. for CuHzzClNO: Cl, 16.13. Found: C1, 16.30.

PREPARATION 5. y-SP1R0[CYCLOHEXANE-1,2-PYRR0LIDYL- 1']-PROPANOLFollowing the procedure of Preparation 4, but employing 27.84 grams (0.2mole) of spiro[cyclohexane-1,2'- pyrrolidine] and 18.9 grams (0.2 mole)of trimethylene chlorohydrin, there was thus obtained 23.43 grams of'y-spiro[cyclohexane-l,2-pyrrolidyl-l]-propanol distilling at 155degrees centigrade at an absolute pressure of 11.5 millimeters ofmercury, having an n of 1.4979 and the analysis below.

Calculated for C12H23NO: N, 7.10; Found: N, 7.12.

Example 1.;3 Spirolcyclohexane 1,2 pyrrolidyl- 1'] ethyl or n propylcyclopentane acetate, hydro chloride and methobromide 1 To a solution of9.33 grams (0.05 mole) of ft-spiro- [cyclohexane 1,2 pyrrolidyl 1']ethanol in fifty milliliters of dry benzene was added 11.3 grams ofu-n-propylcyclopentane-acetyl chloride [Moffett et al., J. Org. Chem.15, 343 (1950)]. A white precipitate appeared almost immediately butredissolved on heating the mixture at its refluxing temperature forthreehours. The solution was maintained at room temperature for abouteighteen hours and then mixed with thirty milliliters of aqueous tenpercent sodium hydroxide. The organic layer was extracted thoroughlywith ether which was then washed with water. The solution was dried, theether distilled and the residue distilled at reduced pressure. An 8.34gram fraction of p spiro [cyclohexane 1,2 pyrrolidyl 1'] ethylorn-propyl-cyclopentane-acetate boiling at 146 to 147 deg'reescentigrade at an absolute pressure of 0.04 millimeter of, mercury wasobtained.

The product thus obtained was dissolved in ether and the solutionacidified with ethanolic hydrogen chloride. The B spiro[cyclohexane 1,2pyrrolidyl 1'] ethyl ot'-n-propyl-cyclopentane-acetate hydrochloridethus obtained, after separation from the solvent, weighed 8.2 grams,melted at 151 to 152 degrees centigrade and had the analysis below.

Calcd. for C21H38C1NO2I C, 67.80; H, 10.30; Cl, 9.53. Found: C, 68.21;H, 10.16; Cl, 9.53.

Additional free base was obtained by making alkaline the filtrateobtained from the filtration of the hydrochloride, separating theprecipitated base and mixing it with the high-. and lower-boilingfractions recovered from the distillation described above andredistilling the whole.

There was thus obtained seven grams of p-spirolcycloroom temperature.The precipitated fl-spiro[cyclohexane-' 1,2 pyrrolidyl 1'] ethyl u npropyl cyelopentane--,

acetate methobromide, after filtering and drying, weighed 5.06 grams,melted at 152 to 154 degrees centigrade and had the analysis below.

Calcd. for CzzHmBrNOz: C, 61.38; H, 9.37; Br, 18.57..

Foundi C, 61.64; H, 9.34; Br, 18.58.

Example 2.--p Spirolcyclohexane 1,2 pyrrolidyl-1']- ethyl or g phenyl Acyclopentene acetate, hydrochlo ride and methobromide Following theprocedure described above for the prep aration of ,8 spiroEcyclohexane1,2 pyrrolidyl 1']- ethyl a'-n-propyl-cyclopentane-acetate, but using11.6 grams of ,8 spiroEcyclohexane 1,2 pyrrolidyl 1']- ethanol and 15.5grams of a-phenyl-A -cyclopentene-acetyl chloride [Horclois, Chemie andIndustrie, Special No., pages 357-63 (April 1934)] in fifty millilitersof dry benzene, there was obtained 22.17 grams, a yield of percent ofthe theoretical, of S-spiroicyclohexane-LT- pyrrolidyl 1'] ethyl orphenyl A cyclopentene-acetate boiling at 163 degrees centigrade'at anabsolute pressure of 0.01 millimeter of mercury and having the analysisbelow.

Calcd. for C24H33N022 C, 78.43; H, 9.05; N, 3.81. Found: C, 78.80; H,8.88; N, 3.84.

A solution of 16.3 grams of the free base obtained as described above indry ether was acidified with ethanolic hydrogen chloride. An oil wasobtained which crystallized from ethyl acetate to give 12.7 grams offi-spiro[cyclohexane 1,2 pyrrolidyl 1'] ethyl a phenyl A-cyclopentene-acetate hydrochloride melting at to 142 degrees centigradeand having the analysis below.

Calcd. for C24Ha4ClNO2: C, 71.33; H, 8.48; Cl, 8.78.

Found: C, 71.31; H, 8.37; Cl, 8.96.

A cold solution of 4.55 grams of the free base obtained as describedabove in 25 milliliters of methyl ethyl ketone was mixed with five gramsof cold methyl bromide. The tightly stoppered flask was maintained atroom temperature for five days. The white crystals ofB-spiroEcyclohexane-1,2'-pyrrolidyl-l'] -ethyl aphenyl-A -cyclopenteneacetate methobromide were separated and, after washing with methyl ethylketone and then with absolute ether, weighed five grams and melted at167.5 to 169 degrees centigrade and had the analysis below.

Calcd. for CzsHseBrNOz: C, 64.92; H, 7.85; Br, 17.28. Found: C, 65.01;H, 7.98; Br, 17.49.

Example 3.B Spiroicyclohexane 1,2 pyrrolidyl 1'] -ethyla-phenyl-cyclopentane-acetate hydrochloride A solution of 9.47 grams(0.0234 mole) of tispiro [cyclohexane-l ,2'-pyrrolidyl-1] -ethyla'-phenyl-A cyclopentene-acetate hydrochloride in milliliters of 95percent ethanol was hydrogenated at room temperature at a pressure offorty pounds in excess of atmospheric pressure in the presence of 0.1gram of platinum oxide catalyst. The theoretical amount of hydrogen wasabsorbed within ten minutes. The solution was filtered and the filtratedistilled nearly to dryness below forty degrees centigrade at reducedpressure. The residue was dissolved in ethyl acetate and crystallizedtherefrom by the addition of ether. The white crystalline precipitatewas filtered, Washed with ether and dried to give 7.88 grams offi-spiro[cyclohexane-1,2-pyrrolidyl-1l-ethyloc'-phenylcyclopentane-acetate hydrochloride melting at 152 to 153.5degrees centigrade and having the analysis below.

Calcd. for C24H3sClNO2:- C, 70.99; H, 8.94; Cl,,8.73. Found: C, 71.21;H, 8.88; Cl, 8.77.

Following the procedure of Example 1 above, diethylacetylchloride can besubstituted for a-n-propyl cyclopentane acetylchloride to producefi-spiro[cyclohexanel,2' -pyrrolidyl-11-ethyl a-diethylacetate,' thehydrochloride and the methobromide salts. Likewise, dicyclohexylacetylchloride and dicyclopentyl-acetyl chloride can be substituted in asimilar manner to produce the corresponding M-dicyclohexyl-acetate, andthe oU-dicyclopentylacetate, respectively, and their correspondinghydrochloride and methobromide salts.

In the same manner, proceeding according to Example 1, but using insteadB-spiro[4'-methylcyclohexane-1,2- pyrrolidyl-1-]'-ethanol anddibutyl-acetyl chloride, 3- spiro[4-methy1cyclohexane-l ,2-pyrrolidyl-1]-ethyl m'-dibutyl-acetate, the hydrochloride and the methobromide,respectively, can be produced. Likewise, substituting fispiro[5'-'methylcyclohexane 1,2 pyrrolidyl 1'] ethanol anda,a-dipropyl-acetylchloride, one can produce B spiro[5 methylcyclohexane 1,2 pyrrolidyl IJ-ethyl a-dipropyl-acetate, thecorresponding hydrochloride and methobromide.

By reacting the novel spiro[cycloalkane-1,2'-pyrrolidyl- 1]-alkyl estersof disubstituted acetic acids of this invention, preferably in the formof the free base in an inert reaction medium with hydrogen peroxide, theamine oxides can be produced. Reacting these amine oxides with an acidin an inert reaction medium, e. g., hydrochloric, hydrobromic,hydriodic, sulfuric, phosphoric, acetic, propionic, benzoic, citric,succinic, lactic, nitric, or p-toluenesulfonic acid, is productive ofthe amine oxide-acid addition salts.

As stated above, the novel esters of this invention, as well as theirhydrohalide or other acid addition salts such as salts withsulfuric,phosphoric, acetic, propionic, benzoic, citric, succinic, lactic,nitric, p-toluenesulfonic, and other acids exhibit pronounced uterinestimulation, for example, the hydrochloride salt of the compound ofExample 2, i. e., fi-spiro[cyclohexane-1,2-pyrrolidyl-l']- ethyla'-phenyl-A -cyclopentene-acetate hydrochloride assayed by the method ofClary, Cameron, and Craver, Proc. Soc. Exptl. Biol. and Med. 77, 778(1951). The novel salt produced pronounced uterine stimulation for fivehours while showing poor anticholinergic activity in the Thiry-Vellaloop dog.

The compounds of this invention have been found to exhibit goodganglionic activity without appreciable antichlorinergic action, when inthe form of, their quaternary ammonium salts; thus the methobromide saltof Example 2 is a good ganglionic blocking agent. It also has been foundto be a moderately active coronary dilator.

It is to be understood that the invention is not to be limited to theexact details of operation or exact compounds shown and described, asobvious modifications and equivalents will be apparent to one skilled inthe art, and the invention is therefore to be limited only by the scopeof the appended claims.

I claim:

1. A compound of the following structural formula:

wherein A and B are hydrocarbon radicals of from one to twelve carbonatoms, inclusive, each of R and R is a member of the group consisting ofhydrogen and methyl, m is a whole number from one to two, inclusive, 1:is a whole number from two to six, inclusive, and CnHzn-- is alower-alkylene group containing at least two'carbon atoms between thevalences.

8 2. 18 Spiro[cyclohexane-1,2'lpyrrolidyl-lJ-ethylan-propyl-cyclopentane-acetate of the following formula:

Cg: (fi CH2 CH2 H: CHJCH2CH1 3. ,B Spiro[cyclohexane-1,2'-pyrrolidyl 1']ethyl or"- phenyl-A cyclopentene-acetate free base of the followingformula:

4. [i Spiro[cyclohexane-l,2'-pyrrolidyl 1'] ethyl a'-phenyl-cyclopentane-acetate of the following formula:

5. An acid addition salt of {i-spiro[cyclohexane-1,2'- pyrrolidyl-l '1-ethyl a-phenyl-A -cyclopentene-acetate;

6. p Spiro[cyclohexane-l,2-pyrollidyl 1'] ethyl 1-phenyl-M-cyclopentene-acetale hydrochloride.

7. ,3 Spiro[cyclohexane-1,2'-pyrollidy1 1'] ethyl aphenyI-A-cyclopentene-acetate methobromide.

8. The method of producing novel spirolcycloalkane-1,2pyrrolidyl-1]-alkyl esters of disubstituted acetic acid comprisingesterifying a Z-spiropyrrolidylalkanol of the formula:

wherein A and B are hydrocarbon radicals of from one to twelve carbonatoms, inclusive, and X is a member of the group consisting of chlorineand bromine.

References Cited in the file of this patent UNITED STATES PATENTS Cusicet a1 Aug. 14, 1951

1. A COMPOUND OF THE FOLLOWING STRUCTURAL FORMULA: